2019
DOI: 10.1002/jbmr.3692
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SiMPLOD, a Structure-Integrated Database of Collagen Lysyl Hydroxylase (LH/PLOD) Enzyme Variants

Abstract: PLOD genes encode for procollagen lysyl hydroxylase enzymes (LH/PLOD), a family of proteins essential for collagen biosynthesis. Several mutations affect these genes, causing severe disorders, such as Ehlers‐Danlos and Bruck syndrome, as well a connective tissue disease with phenotype resembling osteogenesis imperfecta caused by lack of LH3 functions. The recently determined three‐dimensional (3D) structures of the full‐length human LH3/PLOD3 isoform, together with the structure of a fragment of a viral LH/PLO… Show more

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Cited by 23 publications
(14 citation statements)
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“…CAF LH2 depletion prevented collagen gel stiffening and prevented collagen-mediated tumor cell invasion and LH2-mediated collagen cross-links correlated with human breast tumor aggression and poor patient survival [43,158]. Although no specific small molecule inhibitors against LH2 other than Minoxidil exist [159], the development of 3D structure models and a high throughput assay for LH2 activity should accelerate the identification of anti-LH2 compounds [160,161].…”
Section: Targeting the Ecm And Ecm Modulatorsmentioning
confidence: 99%
“…CAF LH2 depletion prevented collagen gel stiffening and prevented collagen-mediated tumor cell invasion and LH2-mediated collagen cross-links correlated with human breast tumor aggression and poor patient survival [43,158]. Although no specific small molecule inhibitors against LH2 other than Minoxidil exist [159], the development of 3D structure models and a high throughput assay for LH2 activity should accelerate the identification of anti-LH2 compounds [160,161].…”
Section: Targeting the Ecm And Ecm Modulatorsmentioning
confidence: 99%
“…[173] The crystal structure of LH3, first of any collagen prolyl or lysyl hydroxylase, will facilitate studies of the molecular mechanisms involved in the LH, GT and GGT activities of this enzyme in the future [151] and has already enabled the development of an online tool for visualization of the molecular level effects of LH mutations. [174] An increasing amount of evidence suggests that LHs are part of larger complexes with chaperones and other proteins [122,175,176] potentially providing an intricate link to effects beyond lysine modifications. In line with this, chaperone and enzyme deficiencies can phenocopy each other as seen with LH1 and FKBP22 and with LH2 and FKBP65.…”
Section: Lysyl Hydrox Yl Ation and Hydrox Ylys Ine G Lycosyl Ationmentioning
confidence: 99%
“…[ 173] The crystal structure of LH3, first of any collagen prolyl or lysyl hydroxylase, will facilitate studies of the molecular mechanisms involved in the LH, GT and GGT activities of this enzyme in the future [ 151] and has already enabled the development of an online tool for visualization of the molecular level effects of LH mutations. [ 174] …”
Section: Lysyl Hydroxylation and Hydroxylysine Glycosylationmentioning
confidence: 99%
“…The expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) is essential for the biosynthesis of collagen and gene mutations thereof, and are related to disorders of the connective tissue [ 1 , 2 , 3 ]. Clinical related mutations with reduced expressions of the PLOD family are associated with the Ehlers-Danlos and Bruck syndromes [ 4 , 5 , 6 ]. PLOD3 alterations during tissue repair might, thus, lead to epithelial–mesenchymal transition (EMT).…”
Section: Introductionmentioning
confidence: 99%